rs10778724

Variant names:

• chr12-80318152-C-T
• rs10778724
• NM_001378609.3:c.3635-394C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378609.3(OTOGL):​c.3635-394C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,072 control chromosomes in the GnomAD database, including 61,900 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61900 hom., cov: 31)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• Publications: 1 publications found

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

OTOGL Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 84B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378609.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	NM_001378609.3	MANE Select	c.3635-394C>T		intron	N/A	NP_001365538.2	Q3ZCN5
	OTOGL	NM_001378610.3		c.3635-394C>T		intron	N/A	NP_001365539.2	Q3ZCN5
	OTOGL	NM_173591.7		c.3635-394C>T		intron	N/A	NP_775862.4	Q3ZCN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.3635-394C>T		intron	N/A	ENSP00000447211.2	Q3ZCN5
	OTOGL	ENST00000646859.1		c.3500-394C>T		intron	N/A	ENSP00000496036.1	A0A2R8YF04

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136024 AN: 151954 Hom.: 61874 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.926

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.895 AC: 136108 AN: 152072 Hom.: 61900 Cov.: 31 AF XY: 0.895 AC XY: 66576 AN XY: 74354

African (AFR) AF: 0.721 AC: 29862 AN: 41426

American (AMR) AF: 0.870 AC: 13286 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3379 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4893 AN: 5156

South Asian (SAS) AF: 0.937 AC: 4520 AN: 4822

European-Finnish (FIN) AF: 0.972 AC: 10297 AN: 10598

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66735 AN: 68014

Other (OTH) AF: 0.926 AC: 1951 AN: 2108

Alfa AF: 0.957 Hom.: 33647

Bravo AF: 0.880

Asia WGS AF: 0.923 AC: 3213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10778724; hg19: chr12-80711932;